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Randomized Controlled Trial
. 2021 Sep;38(9):e14634.
doi: 10.1111/dme.14634. Epub 2021 Jul 18.

Urinary peptidome and diabetic retinopathy in the DIRECT-Protect 1 and 2 trials

Viktor Rotbain Curovic  1 , Pedro Magalhães  2 , Tianlin He  2   3 , Tine W Hansen  1 , Harald Mischak  2 , Peter Rossing  1   4 ; DIRECT Programme Study Group
Affiliations
Randomized Controlled Trial

Urinary peptidome and diabetic retinopathy in the DIRECT-Protect 1 and 2 trials

Viktor Rotbain Curovic et al. Diabet Med. 2021 Sep.

Abstract

Background: Given the association of diabetic retinopathy (DR) and kidney disease, we investigated the urinary peptidome to presence and deterioration of DR in a post hoc analysis of trials investigating the effect of candesartan on progression of DR in type 1 and type 2 diabetes, respectively.

Methods: Baseline urinary peptidomic analysis was performed on a random selection of 783 and 792 subjects in two randomized controlled trials, DIRECT-Protect 1 and 2, respectively. End points were two-step (RET2) and three-step (RET3) change in Early Treatment of Diabetic Retinopathy Study protocol (ETDRS) defined level. Peptide levels were correlated to baseline EDTRS level in a discovery set of 2/3 of the participants from DIRECT-Protect 1. The identified peptides were then validated cross-sectionally in the remaining 1/3 from DIRECT-Protect 1. Thereafter, peptides identified in the discovery set were assessed in the entire DIRECT-Protect 1 and 2 cohorts and significant peptides were tested longitudinally.

Results: Follow-up ranged 4.0-4.7 years. 24 peptides were associated with baseline DR in the discovery set. COL3A1 (seq: NTG~) and COL4A1 (seq: DGA~) were associated with baseline DR in the validation set (Rho: -.223, p < 0.001 and Rho: -.141, p = 0.024). Neither was significantly associated with end points. Assessing the 24 identified peptides in the entire cohorts, several collagen peptides were associated with baseline DR and end points; however, there was no overlap across diabetes types.

Conclusions: We identified several urinary peptides (mainly collagen) associated with the presence of DR, however they could not be conclusively associated with worsening of DR.

Keywords: clinical diabetes; clinical trials; nephropathy; peptidomics; retinopathy.

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References

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